The major objective of this study is to develop biochemical and immunological markers for analysis of the stages of premalignancy of epithelial cells grown from benign colonic adenomas in man. Monolayers of human colonic epithelial cells, cultured from the human adenomas, are used as model systems. The markers to be developed and characterized in these cells include: (1) the expression of fetal-specific antigens; (2) the expression of antigens common to human colon carcinomas and derived cell lines; and (3) the secretion of a protease, possibly a plasminogen activator. Antigen expression will be assayed by either indirect immunofluorescence or the unlabeled antibody peroxidase-antiperoxidase method. Other characteristics of premalignant epithelial cells to be studied include colony formation on adherent versus nonadherent substrates, and reactivity by colony formation to combinations of growth factors. A second, correlative objective is to identify factors which influence the growth of these benign neoplasms, and which may increase the probability of their translation to a stage having more malignant potential. These factors include the well-described promoting agents, the phorbol esters; other suspected promoting agents such as bile acids; retinoic acid, which is an anti-promoter in some systems; and direct-acting carcinogens.